Water soluble organic arsenic and antimony compounds and process of making the same



" wIL ELMjKo E, OF FRANKFOR'lf-ON-THEMAIN, JULIUS HALLENSLELBEN, on noel-ism;

, ON-THE-MAIN; AND-KARLsTREITwoLF AND HUGO BAUERfOF FRANKFURT-N4 i j H v ASSIGNMENTS; To wm'rnnor -CHEMIGALICOMPANY;OFNEW?YORK; N.*Y., ACOBPQRATION OF NEW goingj y WAT R ESQLUBLE QBGANlC' T ARSENICLAND ,ANTIMONY: COMPOUNDS AND PBocEssoF R Y MAKI'NG THESAME No iaiewi g; A piictitifbn ti d pa e Q lPaten ted July 1931 f TH -MAIN; v 'ienmvmn'y'," ASSIGNOBS,

WVehzivefoundthat wttter+solublearsenic and antimony com ounded excellent I cities, are obtained by causing ethylene-oxide," "epihy drinalcohoh A iomonioghgm, 7;,

, or; homologues or; derivatives thereof to act 1 i arsenobenzenes stlblobenzenes' v and larsenostlbiob-enzenesand bl 1611 arsenic and stibonic acids, containingone or several,

amino groups. I

i Besides the above mentioned residues there may also b'e introduced into the molecule any then the sugars tzige offbeing readily solublej 'and of "being well col .kinds of, sugars by reacting s'imulta' neousl or. consecutively, 1 alcohol or the likean'd, besides this,

kinds of sugars for instgtncevvith epihydi'in with any such a manner thet' the epihydrinf a similar body is I first caused to r ac and stibstituent ithe residue of the ethylene oxide "oi-1f its homolognes zisf Well asth residue of v sugars. 1 )These compounds have the adv'an- "bacterisfiprodncingsyphilis,4. v

sslbwbemnerhe egjiggiisssistdb heatin -1 to 65 one ermine group;

i e ibindu oxides and by compounds, being extremely j soluble andbe' converted into arsenoor tionsz- 3v YMVESNE wherein R stands for 'H,

Whichin'zty Etlsofdifier from each other, the "reaction being 'conducted in r Q Y eiversm lhus corn- P llnd whi h ares i bl 1n i at' w h ne. i-, ,tritlfreaction are obtained "which contain as" 25 .tions of common salt and for fwater)',' iThe reaction is fcoinplete as soon es a testsampleldrawn from the product :re--', mains clear 'when "treated with e a solution v it.4t-dil iydroxy-3.3-f aminoarsenobenzene-dirdihydroxypropanei is 1 precipitated .With alcohoh e 7 preparation shoWs'a;yell'oiv 'colour Land is f 4 i QThe reactioncan 111' this case the bythe equivalent 12.905 7 v, 5 readily s'oliible in vvater.

alsobeeifected-in Water. I methyl alcohol is replaced the formula grouping +SbI-Igcans present time be prepared. The are 'soluble in Water "and in'sohiyellowish to products gray partly hygroscopicfpo'wders.*

" The following examples illustrate 5min- I-vention':.=; I J v y I e (1)" 18.3 g'r. of 4A-hydroxy-3l3f-diern+ inoa rsenobenzenel'ere suspended in ;ccm'.=of" l methyl. alcohol and to the suspension there are then added"8;8 gr; Thissuspnsidh'i szillowcd to stand in an at- I 'iFinally;insteadbfthe.arsenobenzenes and f m 9 f v tqq le 1 d1ssolved, 1f necesserythe reaction is to, be

(The res ilting intermediate productis probably a monoaddition productof the oxides nsed; .The' i productissoli ble'inmethyl alcohol, less soluf 5 ble in ethyl 5 alcohol and scarcely soh blein of common salt, The

-0H3; i I stands'for'aldoh'exose residues 3 and Y1 standsfor As or Sb'in a trivalent or and ether. jThe 5542151923, Seria1'No,-683,074,'and in Germany December 27, 1922. I r V quinq'uevalent condition exceptthe rouping SbH Compounds in which according to y given in'the foregoing equa alcdholrbry tions stands for the of epihy rin alcohol;

I I ,c ommonsolt Y 10,

' T ena ik f odi m/a ed ss vedrin 30c f Wa a d t6 liis b iti neera e g f 1 ni hy l'c oljei dfi p a p ydr l oh heiw iQ iW h;m y-be as te y h at ne-W isfi mplet i vsi o oa ai WmP 7 V. rawn m herrq hi how 1 swam-y I iqi To the dif l 8 1 1 unalt red r i V isonicg aeid oh the odditiongof solution of in e hdele ho -a The aqueous solutlons of the above men;

t -iorred ursonimderivaiqlvesf are partly ,dis-' tinquished by oneminehtist ability andere;

intended to be used foriih erapeutical pur Jposes. The product hasthe formula:

'; heated on the, afi 6 0f 'f until' itis dissolved and the reaction-product isrprecipi- 'tate-d from epihydrin'alcohol'iend aminoreadily 'solubleii'rwacehg V phenylstibonic' acid withjaICohol and. ether, i The product thus obtained is a'grey g der,

smo

nostibiobenzene arejdissolved in 7 gqof 1caus-} i t es1o l solutionj fq3 r g x i z ,w'ith 200cm. :of Water. To this solutionfareh I g1 nicr-firhe'fraigct.j1

mee'hsv of alcohol 311d, etHer -the "precipitate tioriis allowed iio stajnd uriltilftheig dditiion of;v afsohition of common salt does not zcause 5' further precipitatio in the' re aetion he sodium; a t i he 4-:hy r y s-am1n X r heph n e ic 7 c d is; rm i ite w h 'ai w l and, he Tins saltas Well flieye'ia'cld 15s 3 g: j of "epihydrin alc hol Theorj acti wn ri s completeas' soon :isthefadditiori 01 a solul t io zof n s t does not" 'm W yg P precipitation in the liquid. The preparation pre ip t t d With alcohola nd ether :g lnd i 1 oluble in waterfiThep d t hasthe I 1 i s i ii .7 l losu pend d ie @9 1 iwater and to. this $113 qension are addedabout 14 g, of epihydrin aleohol; The Whole is then" Qthe formula: V

-NHICHLCHQHCHZIOHI 001113004111 14;) 5,68 (5f the rbein gelearlysoluble in wateri i The prodl lotl ha 'stheforrnula: a I i mnoiriononomo meoniouonemofi L (11*) 1031 gpfof 3l 3 diaihino-i4c diohy-i drogyorsenostibiobenzene are 'diss olvedin7 g. I 5 i I of caustic soda solution of 36% strerigth and i 3 I i com; of water. I Tothi'sf solution are: added i cleziriy, ,for nul'a-z NHjoHiCHo bmdH droxyi-3.3o-diaminoarsenobertzene, dissolved? g1peose."] By the additionof'24; ceni'. ofd i1ble j s normal emisbiqs'oda sohltitiniheire' base"; i fi'sjprecipiteted. "To this mixft'iirefare' added in sma lport e s 'Q f pihy rinl l hbll I wh le a ingr 40 'aiidst r T1 7 a clear yellow solution is, obtziiiied wh'iehjis 1 13 ;10 of the hydrochloride of ir-Bis! 1 methylaminosfir5.5? tetraminoarsenobe -5 jfzene, dissolved in 150 Gem. of ater are mixed I f' with 33.3 ccm ofdouble-rlormal causticfsoda free beis e, ,After havingadde d 221g; 0 g1 .cosQ ,fihre a'rejflirther added om; offepihydrin' alcohol 'i'nfisniall portionhile stirring a solid form. lt theri forms a Which-{contains 20% arid Tether the? substance can be, obtained in of eirserlie.Q prod-'1 hydroehloridejof V I me I i I precipitated by introdlieing itintofag j mixg' Q o 1 i yellowfpowdeii a bniene are dissowed in 50 qcnii of was and the base is precipitated with-about I is.

com; of caustic soda solution of 20% strength. This base is filtered off andafter.

being wel-l dried by suction it is introduced into 30 com. of methylIalcohol' and there are; then added 1.5-1.7 com. of epihydrin alco-' hol. The base turns into .asolution and is then precipitated ithether; if required the reaction is assistedby heating'to 6O. The preparation thus" obtained is almost insolu ble inater. i

I "ggof'the reactron product obtained as above indicated from hydrochloride of 414 :bismethylamino 3 3" 5 -tetraminoarseno- I benzene and epihydrin alcohol are subjected toreactionwith 2.7g. of galactose in methyl by adding ether andxthe substance thus obe tained formsa drin alcohol and 30 com, of ater: and. the Whole is heated to 609 (Iuntil it is dissolved.

This solution is filtered. and the reaction prod? not precipitated with ether. If desired'this I preparation maybe dissolved in alcohol and subsequently re-p-recipitat'ed with ether;

. 340.5 g. of the reaction product obtained fromepihydrin alcohol'aiid 4.4"hydroxy 3l3 I I dian1-inoarsenobenzene asaboye indicated are i I e H I I V ;(18) 18.5 g. of 4-hydroxy-3 aminobenzene tose in ,75' com; ofwater until, a test-sample drawn from the product remains clear when treated Witha solutionof common salt. I The a r the hydrochloride of 4.4%

ed 120 com. of ater-rare linked with 24' I g o-f galactose." f By addinQ Q L ccmnofdoubl'ek eo normal caustic soda solutioni'thefree base is V precipitated, 'To -thevrnixturelare added 3 com; of propylene oxide and the-'Whole'i's heated, to l )'.50 C. Whi1 e stirring and cool- -ing'-in the reflux apparatus, Thus a clear yellow solution is obtainedflwhich is precipipreparation forms a yellow 'powder which' is readilyvsoluble in Water. The product has the formula: v I

c nr on. I

NH.CH2.GHOH.CH2OH II I yellow powder containing 20%"ofarsenic'. v I f (15) '37 g. of Mlze-hydroxy 3.3-diaminoarsenobenzene are introduced into a mixture of 150 ccm; of methyl alcohol, 7.4kccm; ofepihy- 'tain'ed which possess analog arsenous oxide are introduced into ,50 g. of

methylalcoholland there are then addedI' accelerated' by heating to l The-reaction about 12 gbfepihydrih alcohol' This min ture is allowed to stand'unt'il the reaction is s Ycomplete, *There'action may-"eyentually'be is complete as soon as, a test-sample'shows 1110} V precipitation on addition ofa solution of com mon salt. It is then filtered "and the substance dissolved in the filtrate,- is" precipitated by means of ether; The precipitated substance 'is filtered off and dried. The preparation thus obtained is clearly soluble-in Water." Instead' of a free base the hydrochloride mayals be used. a 7 7 V.

formula: I r I j 7 a I i If in the place of the arsenous" oxide and equimolecular quantity of aminobenz'enesti binous oxide is used, preparations are ob-' I The product has theformula j a r-sine are dissolved'in 40,6? gof ethyl alcohol The "above-described product has "the;

and'to-t'his solution 8,1 g. of epihydrin alcohol under othermolecular-proportions; there: are r I also obtained readily soluble products,

' Having now. described our inventionwhatf 1; As new-products the compounds of the, general formulaz v f I c Y wherein Bi and R represents As or Sb, X represents H, CH or CH DH, :Y represents hydrogen, hydroxy, alkoxy, amino or sub I stituted amino and -Z represents hydrogen, 'aminoori substitutedamino. r i w 2. As newfbdi1ctthdcd1hpofifids ofthe 'generalvformulay 5 Y wherein R I 7 wherein'Rand R represehts'As orSb,Xjrepresents H, CH OI',CH2. OH,,Y represents 7 I f -a1koxy,,amino or sub 7 qstituted amino and'Zirepresents the group? 5 hydrogen, hydroxy,

' R and R represent A501 Sb, at leastone'Y I f I whi-ein Rand R repres *oneY'stands foran-am ino' CI-LGHZOH, I I I 0if'CH CHOH. CH and the other Ys repre+ f sentwhydro'gen,'hydr0xy,,a1koxy,' amino or substituted amino, 1;: v

, Intestimony whereof, weiafiix our ign,

' WILHELM KOLLE. i

stahds for an amino the other Ys represubsti tuted ammo;

4,"A's newprpduts cdmlibuhds the 01 plwi g formula:

n15 As or Sb, at least group substituted HZ HOHCHZO 'a 1 .DR. JULIUS" HALLENSLEBEN. DR; KARL STREITWOLF.

-HUGQBAUE -x I P d bmp o unds of the 1. "lowing formul standforoxygefi oi the re sidue I sent hydrogen 'hy drqxy, alkoxy,' amino 01 CERTIFICATE OF CORRECTION.

Patent-No. 1,815,979. Granted July 28, 1931, to

WILHELM KOLLE ET AL.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Page 2, after the formula, lines 9% to 98, inclusive, insert the following paragraph: "The proportions of the reacting compounds may be altered to effect substitution of but one amido group"; page 3, lines 74 and 75, for the word "diohydroxyarsenostibiobenzene" read dihydroxyarsenostihiobenzene; and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 3rd day of November, A. D. 1931.

M. J. Moore, (Seal) Acting Commissioner of Patents. 

